Part 1 - Pan Alphavirus Preclinical Testing Viruses of the genus Alphavirus, Family Togaviridae, are single-stranded RNA viruses that are transmitted via insect vectors such as mosquitoes. Western Equine Encephalitis virus (WEEV), Eastern Equine Encephalitis virus (EEEV), and Venezuelan Equine Encephalitis virus (VEEV) are three such zoonotic alphaviruses that cause a potentially fatal encephalitic illness in the horse. For each of these alphaviruses, transmission to humans is possible. Human infection with VEEV results in flu-like symptoms including high fever and muscle aches. People with weakened immune systems and the young and elderly can become severely ill and die from the disease. WEEV is relatively uncommon and often only causes a subclinical infection in humans. EEEV causes a more virulent disease, and has previously resulted in fatal cases of encephalitis in children, coinciding with outbreaks of EEEV in horses. Part 2 - Filovirus Countermeasures Ebola virus is a deadly microbe producing viral hemorrhagic fever (VHF), with lethal results in the vast majority of infected individuals. The onset of Ebola hemorrhagic fever is abrupt and is characterized by the sudden onset of fever, weakness, muscle pain, headache, and sore throat, followed by vomiting, diarrhea, rash, both internal and external bleeding, and often death. While the human exposure route for Ebola virus is unknown, once a person becomes infected, the virus spreads rapidly to other persons in close contact with the infected individual. No vaccines or proven treatments exist for Ebola, a virus that is known to have been [unreadable]weaponized[unreadable], i.e., adapted for use as a bioterrorism agent. Ebola has been categorized as a priority class A pathogen due to its virulence, ease of dissemination, and lack of effective countermeasures to prevent or treat disease. This project describes the use of drugs that target tyrosine kinases (TK) to prevent disease from Ebola. Part 3 - HIV, Influenza, Alphavirus and Other Biodefense Pathogen Countermeasures Support for the Dale and Betty Bumpers Vaccine Research Center (VRC) at the National Institutes of Health to facilitate research in vaccine development. The VRC is dedicated to improving global human health through the rigorous pursuit of effective vaccines for human diseases.